betadex and naringenin

In this work, naringenin loaded β-cyclodextrin and carbon quantum dots composite nanoparticles were successfully fabricated. The results showed that incorporation of carbon quantum dots not only enhanced antioxidant activities of nanoparticles but also improved encapsulation efficiency of naringenin. Further, the formation of composite nanoparticles was confirmed by a series of characterization methods. The zeta-potential and Fourier transform infrared spectroscopy data proved that electrostatic interaction and hydrogen bonding are dominant forces to form nanoparticles. X-Ray Diffraction experiment revealed that the material state of the formed naringenin-β-CD-CQDs nanoparticles is amorphous in opposition to the crystalline state of naringenin, β-CD and naringenin-β-CD inclusion complex. Finally, antioxidant activity analyses against DPPH, ABTS

Topics: Antioxidants; beta-Cyclodextrins; Carbon; Flavanones; Nanocomposites; Quantum Dots

The aim of present study was to evaluate the feasibility of a naringenin-hydroxypropyl-β-cyclodextrin (naringenin-HPβCD) inhalation solution for pulmonary delivery. Naringenin, a flavanone derived from citrus fruits, has been proven to exhibit excellent peripheral antitussive effect. To address the limitation of its poor oral bioavailability and low local concentration in the lung, a naringenin-HPβCD inhalation solution was prepared for pulmonary delivery. The aerosolization performance of formulation was evaluated by next generation impactor (NGI). Both dose-dependent and time-dependent antitussive effects of naringenin-HPβCD inhalation solution on acute cough induced by citric acid in guinea pigs were investigated. In vitro toxicity of naringenin-HPβCD inhalation solution in pulmonary Calu-3 cells was evaluated by MTS assay, and in vivo local toxicity investigation was achieved by assessing bronchoalveolar lavage (BALF) and lung histology after a 7-day inhalation treatment in guinea pigs. Fine particle fraction (FPF) of the formulation was determined as 53.09%. After inhalation treatment of 15 min, naringenin-HPβCD inhalation solution within the studied range of 0.2-3.6 mg/kg could dose-dependently reduce the cough frequency with the antitussive rate of 29.42-39.42%. Naringenin-HPβCD inhalation solution in concentration range of 100-400 μM did not decrease cell viability of Calu-3 cells, and the maximum effective dose (3.6 mg/kg) was non-toxic during the short-term inhalation treatment for guinea pigs. In conclusion, naringenin-HPβCD inhalation solution was capable for nebulization and could provide rapid response with reduced dose for the treatment of cough.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Administration, Inhalation; Aerosols; Animals; Antitussive Agents; beta-Cyclodextrins; Biological Availability; Flavanones; Guinea Pigs; Lung

The aim of this study was to prepare and characterize the naringenin-loaded sulfobutylether-β-cyclodextrin/chitosan nanoparticles (Nag-CD/CS-NPs) and evaluate their potential for the topical ophthalmic delivery. Naringenin was first complexed with sulfobutylether-β-cyclodextrin (SBE-β-CD), which can significantly enhance the solubility of poorly soluble drugs. Then, nanoparticles were prepared by ionic gelation of chitosan with SBE-β-CD, and their in vitro and vivo properties were investigated, respectively. The resulting nanoparticles showed an average size of 446.4±112.8nm and zeta potential of +22.5±4.91mV with predominant spherical in shape. The FT-IR and DSC confirmed the formation of Nag-CD/CS-NPs. The in vitro release study indicated that Nag-CD/CS-NPs achieved moderate sustained-release effect, and the in vivo study revealed that the prepared nanoparticles was nonirritating to rabbit's eye and had better ability to prolong the residence time than the naringenin suspension, which can significantly increase naringenin bioavailability in the aqueous humor. In conclusion, the developed CD/CS nanoparticles offer a potential alternative for the ocular administration of poorly soluble drugs.

Topics: Administration, Topical; Animals; beta-Cyclodextrins; Chitosan; Drug Carriers; Drug Liberation; Female; Flavanones; Macular Degeneration; Male; Nanoparticles; Particle Size; Rabbits; Solubility

Cu(II) complexed amino acid ionic liquid, Cu(II)-[1-butyl-3-methylimidazolium][L-Pro] (Cu(II)-[BMIm][L-Pro]), was successfully adopted as chiral ligand to improve the enantioseparation efficiency in high speed counter-current chromatography (HSCCC). For the enantioseparation of intractable naringenin (NRG) racemic mixtures, Cu(II)-[BMIm][L-Pro] coupled with hydroxypropyl-β-cyclodextrin (HP-β-CD) was successfully applied as dual chiral selectors in HSCCC. The influence of important parameters, including the concentration of the chiral selectors, the pH value, and the temperature were investigated. Under optimal conditions, 4.5mg of (+)-NRG and 4.1mg of (-)-NRG were successfully separated from 10mg NRG racemic mixtures with the purity of 98%. The chiral recognition mechanism of dual chiral selectors was illuminated by the UV-vis and NMR spectra, suggesting that the enantioseparation was upon the difference of the thermodynamic stability of the quaternary complexes of Cu(II), [BMIm][L-Pro], HP-β-CD, and NRG. The results illustrated that the developed HSCCC system, based on the synergistic mechanism of Cu(II)-[BMIm][L-Pro] and HP-β-CD, exhibited better performance on enantioseparation and had great application potential in preparative chiral separation of natural products.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Amino Acids; beta-Cyclodextrins; Copper; Countercurrent Distribution; Flavanones; Ionic Liquids; Stereoisomerism; Thermodynamics

The present study evaluated the antioxidant and hepatoprotective effects of the flavonoid naringenin (NGN) and its β-cyclodextrin formulation at a dose of 50 mg/kg b.w. The assessment was done by the investigation of serum-enzymatic and liver antioxidant activity, histopathological and ultrastructural changes in male Swiss mice, which were subjected to acute experimental intoxication with CCl4. Formulated and free flavonoid were orally given to mice for 7 days and then were intraperitoneally injected with 1.0 mL/kg CCl4 on the 8th day. After 24 h of CCl4 administration, an increase in the levels of transaminases aspartate aminotransferase and alanine aminotransferase activities and malondialdehyde concentration occurred and a significant decrease in superoxide dismutase, catalase glutathione-peroxidase activities, and glutathione levels was detected as well. These were accompanied by extended centrilobular necrosis, steatosis, fibrosis, and an altered ultrastructure of hepatocytes. Pretreatment with formulated or free flavonoid retained the biochemical markers to control values. Histopathological and electron-microscopic examination confirmed the biochemical results. In conclusion, both NGN and NGN/β-cyclodextrin complex showed antioxidant and hepatoprotective effects against injuries induced by CCl4.

Topics: Animals; Antioxidants; beta-Cyclodextrins; Cacao; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Citrus; Drug Delivery Systems; Flavanones; Lipid Peroxidation; Liver; Male; Phytotherapy; Plant Extracts; Rats, Wistar; Solanum lycopersicum; Superoxide Dismutase

The structure, dynamic behavior and binding affinity of the inclusion complexes between naringenin and the two cyclodextrins (CDs), β-CD and its 2,6-dimethyl derivative (DM-β-CD), were theoretically studied by multiple molecular dynamics simulations and free energy calculations. Naringenin most likely prefers to bind with CDs through the phenyl ring. Although a lower hydrogen bond formation of naringenin with the 3-hydroxyl group of DM-β-CD (relative to β-CD) was observed, the higher cavity could encapsulate almost the whole naringenin molecule. In contrast for the naringenin/β-CD complex, the phenyl ring feasibly passed through the primary rim resulting in the chromone ring binding inside instead. MM-PBSA/GBSA and QM-PBSA/GBSA binding free energies strongly suggested a greater stability of the naringenin/DM-β-CD inclusion complex. Van der Waals force played an important role as the key guest-host interaction for the complexation between naringenin and each cyclodextrin.

Topics: Adipates; beta-Cyclodextrins; Drug Stability; Flavanones; Molecular Dynamics Simulation; Molecular Structure; Succinates; Thermodynamics

Choroidal neovascularization (CNV) is characterized by abnormal blood vessels growing from the choroid. Current remedies for CNV have not shown favorable therapeutic efficacy. It is urgent to identify and develop more safe and potent anti-CNV agents via multiple technologies. We previously showed that the natural product naringenin attenuated CNV. However, naringenin has poor water solubility and low bioavailability. Here, we prepared the β-cyclodextrin (β-CD) complex of naringenin and characterized it using infrared spectra and X-ray diffraction analyses. Determination of content and solubility in the complex showed that naringenin accounted for 20.53% in the complex and its solubility was increased by more than 10-fold. Using a laser-induced CNV model in rats we demonstrated that naringenin/β-CD complex more significantly reduced CNV area than naringenin alone in rats. Furthermore, naringenin and its β-CD complex significantly inhibited the mRNA and protein expression of VEGF, COX-2, PI3K, p38MAPK, MMP-2, and MMP-9 in retina and choroid tissues. Naringenin/β-CD complex showed more significant inhibitory effect on VEGF and COX-2 expression than naringenin. These results collectively indicated that naringenin/β-CD complex could be a promising therapeutic option for CNV and that the beneficial effects could be linked to the anti-inflammatory properties of naringenin.

Topics: Angiogenesis Inhibitors; Animals; beta-Cyclodextrins; Choroid; Choroidal Neovascularization; Flavanones; Male; Matrix Metalloproteinases; Rats; Signal Transduction; Spectrophotometry, Infrared; Vascular Endothelial Growth Factor A; X-Ray Diffraction

The interaction of naringenin (Nar) and its neohesperidoside, naringin (Narn), with calf thymus deoxyribonucleic acid (ctDNA) in the absence and the presence of β-cyclodextrin (β-CD) was investigated. The interaction of Nar and Narn with β-CD/ctDNA was analyzed by using absorption, fluorescence, and molecular modeling techniques. Docking studies showed the existence of hydrogen bonding, electrostatic and phobic interaction of Nar and Narn with β-CD/DNA. 1:2 stoichiometric inclusion complexes were observed for Nar and Narn with β-CD. With the addition of ctDNA, Nar and Narn resulted into the fluorescence quenching phenomenon in the aqueous solution and β-CD solution. The binding constant K(b) and the number of binding sites were found to be different for Nar and Narn bindings with DNA in aqueous and β-CD solution. The difference is attributed to the structural difference between Nar and Narn with neohesperidoside moiety present in Narn.

Topics: beta-Cyclodextrins; Binding Sites; Chemistry, Pharmaceutical; DNA; Drug Carriers; Flavanones; Hydrogen Bonding; Molecular Docking Simulation; Molecular Structure; Nucleic Acid Conformation; Spectrometry, Fluorescence; Spectrophotometry, Ultraviolet; Static Electricity; Technology, Pharmaceutical

The inclusion complexation behavior, characterization and binding ability of naringenin with β-cyclodextrin and its derivatives were investigated in both solution and the solid state by means of XRD, DSC, SEM, (1)H and 2D NMR and UV-vis spectroscopy. The results showed that the water solubility and thermal stability of naringenin were obviously increased in the inclusion complex with cyclodextrins. This satisfactory water solubility and high thermal stability of the naringenin/CD complexes will be potentially useful for their application as herbal medicines or healthcare products.

Topics: beta-Cyclodextrins; Biological Availability; Flavanones; Solubility; Water

To determine the major factors affecting the conversion efficiency of naringin-HP-beta-CD that was enzymed to prepare naringenin were determined and select the process condition with high conversion efficiency, stable and suitable for industrial production.. The dropping method was used to prepare naringin-HP-beta-CD, which was hydrolyzed by snailase to obtain naringenin. With the bioconversion rate as the index, the effects of pH value, temperature, reaction time, dosage of enzyme and concentration of naringin-HP-beta-CD on conversion rate of naringenin were detected for the purpose of optimizing the preparation condition. the conversion efficiency of naringin-HP-beta-CD was verified by scanning calorimetry, and the Hydrolysis product was identified by H-NMR, and 13C-NMR.. The optimum enzymolysis of naringin-HP-beta-CD with snailase was 98.4% under the conditions of 37 degrees C, a pH 5.0 acetic acid- sodium acetate buffer solution for 12 hours. The substrate concentration was 30 g x L(-1) and the weight ratio of enzyme and substrate was 3: 5. Under the optimum enzymolysis condition, the conversion rate of naringin-HP-beta-CD was higher than naringin that was not entrapped with HP-beta-CD, with 272.25 reaction product relative molecules. The structure of naringenin was confirmed by the analysis of 1H-NMR and 13C-NMR.. Naringin which is entrapped with HP-beta-CD to prepare naringenin can significantly improve the conversion efficiency by shortening the reaction time, increasing the concentration of the substrate and reducing the amount of enzyme. Therefore, the process is stable and it was suitable for industrialization.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; beta-Cyclodextrins; Flavanones; Hydrolysis; Solubility

The abundant flavonoid aglycone, naringenin, which is responsible for the bitter taste in grapefruits, has been shown to possess hypolipidemic and anti-inflammatory effects both in vitro and in vivo. Recently, our group demonstrated that naringenin inhibits hepatitis C virus (HCV) production, while others demonstrated its potential in the treatment of hyperlipidemia and diabetes. However, naringenin suffers from low oral bioavailability critically limiting its clinical potential. In this study, we demonstrate that the solubility of naringenin is enhanced by complexation with β-cyclodextrin, an FDA approved excipient. Hydroxypropoyl-β-cyclodextrin (HPβCD), specifically, increased the solubility of naringenin by over 400-fold, and its transport across a Caco-2 model of the gut epithelium by 11-fold. Complexation of naringenin with HPβCD increased its plasma concentrations when fed to rats, with AUC values increasing by 7.4-fold and C(max) increasing 14.6-fold. Moreover, when the complex was administered just prior to a meal it decreased VLDL levels by 42% and increased the rate of glucose clearance by 64% compared to naringenin alone. These effects correlated with increased expression of the PPAR co-activator, PGC1α in both liver and skeletal muscle. Histology and blood chemistry analysis indicated this route of administration was not associated with damage to the intestine, kidney, or liver. These results suggest that the complexation of naringenin with HPβCD is a viable option for the oral delivery of naringenin as a therapeutic entity with applications in the treatment of dyslipidemia, diabetes, and HCV infection.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Administration, Oral; Animals; beta-Cyclodextrins; Biological Availability; Biological Transport; Body Weight; Caco-2 Cells; Diet; Flavanones; Glucose; Humans; Lipoproteins, VLDL; Male; Rats; Rats, Sprague-Dawley; Solubility; Solutions

In this study a complex of naringenin with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was prepared to improve the hydrophilicity of naringenin. The physicochemical properties of the complex were analyzed by ultraviolet-visible spectrometry (UV), infrared spectrometry (IR), X-ray diffractometry (XRD), differential scanning calorimetry (DSC). The result showed that naringenin had been molecularly dispersed in the HP-beta-CD matrix, not forming a new compound and HPLC analysis showed that the solubility of naringenin in water was enhanced from 4.38 microg/mL to 1,272.31 microg/mL.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; beta-Cyclodextrins; Calorimetry, Differential Scanning; Flavanones; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet; X-Ray Diffraction